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Engineered peptide PLG0206 overcomes limitations of a challenging antimicrobial drug class
The absence of novel antibiotics for drug-resistant and biofilm-associated infections is a global public health crisis. Antimicrobial peptides explored to address this need have encountered significant development challenges associated with size, toxicity, safety profile, and pharmacokinetics. We de...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9481017/ https://www.ncbi.nlm.nih.gov/pubmed/36112657 http://dx.doi.org/10.1371/journal.pone.0274815 |
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author | Huang, David B. Brothers, Kimberly M. Mandell, Jonathan B. Taguchi, Masashi Alexander, Peter G. Parker, Dana M. Shinabarger, Dean Pillar, Chris Morrissey, Ian Hawser, Stephen Ghahramani, Parviz Dobbins, Despina Pachuda, Nicholas Montelaro, Ronald Steckbeck, Jonathan D. Urish, Kenneth L. |
author_facet | Huang, David B. Brothers, Kimberly M. Mandell, Jonathan B. Taguchi, Masashi Alexander, Peter G. Parker, Dana M. Shinabarger, Dean Pillar, Chris Morrissey, Ian Hawser, Stephen Ghahramani, Parviz Dobbins, Despina Pachuda, Nicholas Montelaro, Ronald Steckbeck, Jonathan D. Urish, Kenneth L. |
author_sort | Huang, David B. |
collection | PubMed |
description | The absence of novel antibiotics for drug-resistant and biofilm-associated infections is a global public health crisis. Antimicrobial peptides explored to address this need have encountered significant development challenges associated with size, toxicity, safety profile, and pharmacokinetics. We designed PLG0206, an engineered antimicrobial peptide, to address these limitations. PLG0206 has broad-spectrum activity against >1,200 multidrug-resistant (MDR) ESKAPEE clinical isolates, is rapidly bactericidal, and displays potent anti-biofilm activity against diverse MDR pathogens. PLG0206 displays activity in diverse animal infection models following both systemic (urinary tract infection) and local (prosthetic joint infection) administration. These findings support continuing clinical development of PLG0206 and validate use of rational design for peptide therapeutics to overcome limitations associated with difficult-to-drug pharmaceutical targets. |
format | Online Article Text |
id | pubmed-9481017 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-94810172022-09-17 Engineered peptide PLG0206 overcomes limitations of a challenging antimicrobial drug class Huang, David B. Brothers, Kimberly M. Mandell, Jonathan B. Taguchi, Masashi Alexander, Peter G. Parker, Dana M. Shinabarger, Dean Pillar, Chris Morrissey, Ian Hawser, Stephen Ghahramani, Parviz Dobbins, Despina Pachuda, Nicholas Montelaro, Ronald Steckbeck, Jonathan D. Urish, Kenneth L. PLoS One Research Article The absence of novel antibiotics for drug-resistant and biofilm-associated infections is a global public health crisis. Antimicrobial peptides explored to address this need have encountered significant development challenges associated with size, toxicity, safety profile, and pharmacokinetics. We designed PLG0206, an engineered antimicrobial peptide, to address these limitations. PLG0206 has broad-spectrum activity against >1,200 multidrug-resistant (MDR) ESKAPEE clinical isolates, is rapidly bactericidal, and displays potent anti-biofilm activity against diverse MDR pathogens. PLG0206 displays activity in diverse animal infection models following both systemic (urinary tract infection) and local (prosthetic joint infection) administration. These findings support continuing clinical development of PLG0206 and validate use of rational design for peptide therapeutics to overcome limitations associated with difficult-to-drug pharmaceutical targets. Public Library of Science 2022-09-16 /pmc/articles/PMC9481017/ /pubmed/36112657 http://dx.doi.org/10.1371/journal.pone.0274815 Text en © 2022 Huang et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Huang, David B. Brothers, Kimberly M. Mandell, Jonathan B. Taguchi, Masashi Alexander, Peter G. Parker, Dana M. Shinabarger, Dean Pillar, Chris Morrissey, Ian Hawser, Stephen Ghahramani, Parviz Dobbins, Despina Pachuda, Nicholas Montelaro, Ronald Steckbeck, Jonathan D. Urish, Kenneth L. Engineered peptide PLG0206 overcomes limitations of a challenging antimicrobial drug class |
title | Engineered peptide PLG0206 overcomes limitations of a challenging antimicrobial drug class |
title_full | Engineered peptide PLG0206 overcomes limitations of a challenging antimicrobial drug class |
title_fullStr | Engineered peptide PLG0206 overcomes limitations of a challenging antimicrobial drug class |
title_full_unstemmed | Engineered peptide PLG0206 overcomes limitations of a challenging antimicrobial drug class |
title_short | Engineered peptide PLG0206 overcomes limitations of a challenging antimicrobial drug class |
title_sort | engineered peptide plg0206 overcomes limitations of a challenging antimicrobial drug class |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9481017/ https://www.ncbi.nlm.nih.gov/pubmed/36112657 http://dx.doi.org/10.1371/journal.pone.0274815 |
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